Dataset of EEG power integral, spontaneous recurrent seizure and behavioral responses following combination drug therapy in soman-exposed rats

Abstract

This article investigated the efficacy of the combination of antiepileptic drug therapy in protecting against soman-induced seizure severity, epileptogenesis and performance deficits. Adult male rats with implanted telemetry transmitters for continuous recording of electroencephalographic (EEG) activity were exposed to soman and treated with atropine sulfate and the oxime HI-6 one minute after soman exposure and with midazolam, ketamine and/or valproic acid 40 min after seizure onset. Rats exposed to soman and treated with medical countermeasures were evaluated for survival, seizure severity, the development of spontaneous recurrent seizure and performance deficits; combination anti-epileptic drug therapy was compared with midazolam monotherapy. Telemetry transmitters were used to record EEG activity, and a customized MATLAB algorithm was used to analyze the telemetry data. Survival data, EEG power integral data, spontaneous recurrent seizure data and behavioral data are illustrated in figures and included as raw data. In addition, edf files of one month telemetry recordings from soman-exposed rats treated with delayed midazolam are provided as supplementary materials. Data presented in this article are related to research articles “Rational Polytherapy in the Treatment of Cholinergic Seizures” [1] and “Early polytherapy for benzodiazepine-refractory status epilepticus [4].

Delayed midazolam dose effects against soman in male and female plasma carboxylesterase knockout mice

“…Although several animal models of chemically induced SE have shown that the anticonvulsive effectiveness of benzodiazepines significantly decreases with increasing delay in administration, 37 our current findings demonstrate the benefit to MDZ administration even when treatment is delayed in a human-relevant mouse model. Consistent with our previous observations in rats, 7,11,15 the present study demonstrated that in GD-exposed Es1 −/− mice, MDZ treatment delayed to 40 min after seizure onset was unable to significantly reduce seizure activity, or prevent epilepto-genesis or neuronal loss. The current findings are also in agreement with our previous study in male Es1 −/− mice in which MDZ (5 mg/kg) at 15 min after GD-induced seizure onset was unable to prevent SRS or brain pathology.…”

“…These findings are in agreement with our previous findings in male rats in which MDZ (1-9 mg/kg, IP) at 40 min after GD-induced SE dose-dependently increased survival. 15 Survival data from the present mouse study show that when MDZ treatment is delayed to 40 min after SE onset, a dose of at least 9 mg/kg is needed to obtain a survival percentage (78.6%) that is comparable with the results of survival (66.7%) from a prior study in which 5 mg/kg (IP) of MDZ was administered 15 min after SE in male mice. 20 The current study to include a delay of 40 min for the administration of MDZ after the onset of CWNA-induced seizure is highly relevant to a time point when treatments may be provided by first responders in a mass casualty CWNA attack.…”

“…This finding is similar to previous observations in GDexposed rats in which MDZ (3 mg/kg) reduced power spectral density during the first hour following treatment. 15 In the present study, survival data throughout 14 days following GD-induced SE represent a key contrast from former studies that focused on the lethality effect during the first 24 h after the toxic insult. Although several animal models of chemically induced SE have shown that the anticonvulsive effectiveness of benzodiazepines significantly decreases with increasing delay in administration, 37 our current findings demonstrate the benefit to MDZ administration even when treatment is delayed in a human-relevant mouse model.…”

“…[5][6][7][8] The delayed administration of MDZ or DZP to GD-or sarin-exposed rats does not prevent the development of spontaneous recurrent seizure (SRS), or the brain damage, neuroinflammatory responses, and behavioral deficits caused by CWNA-induced seizure. 3,4,[8][9][10][11][12][13][14][15] However, although delayed MDZ treatment fails to quickly terminate seizure and is not fully neuroprotective, it may reduce seizure severity in the first hour after treatment and dose-dependently reduce mortality compared with rats that were not given MDZ. 3,15,16 Although the rat and other rodent models of GD exposure have traditionally been used for the identification of novel therapies that counteract the aforementioned effects of CWNA-induced SE, the presence of plasma carboxylesterase activity in such animals may confound results.…”

“…3,4,[8][9][10][11][12][13][14][15] However, although delayed MDZ treatment fails to quickly terminate seizure and is not fully neuroprotective, it may reduce seizure severity in the first hour after treatment and dose-dependently reduce mortality compared with rats that were not given MDZ. 3,15,16 Although the rat and other rodent models of GD exposure have traditionally been used for the identification of novel therapies that counteract the aforementioned effects of CWNA-induced SE, the presence of plasma carboxylesterase activity in such animals may confound results. Because GD binds irreversibly to carboxylesterase, it reduces the systemic concentration of the organophosphorus agent that is freely available to inhibit AChE, 17 thereby providing some protection against lethal doses of certain organophosphorus compounds, including GD.…”